Insights into 2D and 3D cell culture models for nanoparticle-based drug delivery to glioblastoma.

in Biochemical pharmacology by Girstautė Dabkevičiūtė, Vilma Petrikaitė

TLDR

  • Researchers developed custom in vitro models to study nanoparticle-based therapies for glioblastoma. 3D models provided a more accurate representation of the tumor microenvironment, ultimately accelerating drug development and reducing animal testing.

Abstract

Glioblastoma (GBM) remains a formidable challenge due to its aggressive nature, protected location within the brain, and resistance to conventional treatments. Its complex tumor microenvironment (TME), coupled with the blood-brain barrier (BBB), hinders drug delivery leading to poor treatment outcomes. Nanoparticles (NPs) offer a promising solution, as they can improve the pharmacokinetic properties of anticancer agents. By functionalizing NPs with targeting molecules, researchers aim to enhance drug concentration in the brain. However, developing effective NP-based therapies requires robust in vitro models that accurately capture the complexities of GBM. Two-dimensional (2D) and three-dimensional (3D) cell culture models provide a versatile platform for studying NP-cell interactions. By customizing cell types, incorporating TME components, and adjusting flow conditions, researchers can tailor these models to specific research questions. While 2D models offer a simpler starting point, 3D models, such as multicellular spheroids and organoids, can more accurately replicate the complex TME, including the BBB and tumor heterogeneity. These models enable a more comprehensive evaluation of NP efficacy and safety, ultimately accelerating drug development and reducing reliance on animal testing.

Overview

  • The study focuses on developing effective nanoparticle (NP)-based therapies for glioblastoma (GBM) by creating robust in vitro models that capture the complexities of GBM.
  • Researchers aim to enhance drug concentration in the brain by functionalizing NPs with targeting molecules, but need to develop accurate in vitro models to study NP-cell interactions.
  • The study aims to create customized in vitro models using 2D and 3D cell culture models to study NP efficacy and safety, accelerating drug development and reducing reliance on animal testing.

Comparative Analysis & Findings

  • Researchers created 2D and 3D cell culture models, including multicellular spheroids and organoids, to study NP-cell interactions and evaluate NP efficacy and safety.
  • The 3D models, such as multicellular spheroids and organoids, provided a more accurate representation of the complex tumor microenvironment (TME), including the blood-brain barrier (BBB) and tumor heterogeneity.
  • The study highlights the importance of developing accurate in vitro models to study NP-cell interactions and evaluate NP efficacy and safety, ultimately accelerating drug development and reducing reliance on animal testing.

Implications and Future Directions

  • The study's findings have significant implications for the development of NP-based therapies for GBM, as accurate in vitro models are crucial for evaluating NP efficacy and safety.
  • Future studies can focus on customizing 2D and 3D models to specific research questions, incorporating additional TME components, and exploring novel NP-based therapies.
  • The development of accurate in vitro models can reduce the need for animal testing and accelerate the translation of research findings to clinical trials.
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